Found 1 Presentation For Request "1060P"

NSCLC, metastatic

1060P - Impact of baseline clinicopathologic and genomic features on outcomes to KRAS G12C inhibitors in patients with NSCLC

Presentation Number
1060P
Speakers
  • Giuseppe Lamberti (Bologna, Italy)
Date
Mon, 12.09.2022

Abstract

Background

Baseline factors that influence efficacy of KRASG12C inhibitors (G12Ci) in patients (pts) with KRASG12C-mutant non-small cell lung cancer (NSCLC) are largely unknown. We sought to identify clinicopathological and genomic features associated with outcome to G12Ci.

Methods

Among pts at the Dana-Farber Cancer Institute and Massachusetts General Hospital with NSCLC who received a G12Ci as monotherapy, baseline clinicopathological and genomic features were correlated with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).

Results

Ninety-two pts received a G12Ci (median age 66.5 years, 63% female): 20 (22%) had an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2, 42 (46%) had history of brain metastases prior to G12Ci start, of which 15 (36%) were untreated before G12Ci initiation. Overall, the ORR was 39% (N=31/80), the median PFS (mPFS) was 5.1 months, and the median OS (mOS) was 9.8 months. Compared to an ECOG PS of 0-1, an ECOG PS of ≥2 was associated with shorter mPFS (5.5 vs 2.5 months, p=0.01) and mOS (12.4 vs 4.9 months, p<0.01). Compared to receipt of a G12Ci in the ≥2nd line, 1st-line treatment was associated with a higher ORR (75% [N=9/13] vs 32% [N=22/68], p=0.01), but line of therapy had no significant impact on mPFS or mOS. Co-occurring genomic alterations included STK11 mutation (mut) in 24 cases (27%), KEAP1 mut in 16 (23%), TP53 mut in 40 (44%), SMARCA4 mut in 9 (13%), ATM mut in 11 (13%), and CDKN2A/B deficiency in 21 (25%). ATM wild-type (wt) compared to ATM mut had lower ORR (33% vs 78%, p=0.02) and shorter mPFS (4.1 vs 13.8 months, p=0.04), but no different mOS. Longer mPFS and mOS were observed in SMARCA4 wt compared to mut (mPFS: 5.9 vs 2.8 months, p=0.02; mOS: 11.3 vs 5.3 months, p=0.02) and in CDKN2A/B intact compared to deficient (mPFS: 5.8 vs 2.8 months, p=0.02; mOS: 11.3 vs 5.7 months, p=0.01). There was no difference in mPFS or mOS according to STK11 or KEAP1 mutational status.

Conclusions

Baseline clinicopathological characteristics may help predict outcome to G12Ci in pts with KRASG12C-mutant NSCLC. Larger series are needed to confirm if co-occurring genomic alterations may help identify pts who derive differential benefit from G12Ci.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Nishino: Financial Interests, Personal, Advisory Role: Daiichi Sankyo, AstraZeneca; Financial Interests, Personal, Research Grant: Merck, Canon Medical Systems, Daiichi Sankyo, AstraZeneca. L.M. Sholl: Financial Interests, Personal, Advisory Role: GV20 Therapeutics, Genentech, Lilly; Financial Interests, Personal, Research Grant: BMS, Genentech. R. Heist: Financial Interests, Personal, Advisory Board: Daichii Sankyo, Novartis, EMD Serono; Financial Interests, Personal, Invited Speaker: Chugai Roche; Financial Interests, Personal, Other, review of cancer histories: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board, consulting honoraria: AbbVie; Financial Interests, Institutional, Invited Speaker: Daichii Sankyo, Novartis, AbbVie, Roche, Incyte, Mirati, Agios, Corvus, Turning Point, Lilly, Exelixis; Non-Financial Interests, Member: IASLC, ASCO, AACR. M. Awad: Financial Interests, Personal, Advisory Role: BMS, AstraZeneca, Achilles, AbbVie, Neon, Maverick, Nektar, Hegrui, Syndax, Gritstone; Financial Interests, Personal, Research Grant: BMS, AstraZeneca, Lilly, Genentech. All other authors have declared no conflicts of interest.

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